The purpose of these studies is to define the types and mechanisms of action of T cells which regulate antibody responses to the so-called thymus-independent (TI) antigens type III pneumococcal polysaccharide (S3) and polyvinylpyrrolidone (PVP). Two distinct subsets of S3-specific suppressor T cells (TS) have been characterized, and current experiments are aimed at determining the mechanism by which these TS suppress the anti-S3 antibody response. One of the S3-specific TS has apparent specificity for S3 plus self I-J determinants, and current studies are aimed at determining whether these TS may be induced by S3 presented on a subset of antigen presenting cells that bear I-J determinants. Recent studies have also established that a contrasuppressor T cell (Tcs) is induced by S3 or by S3-coupled spleen cells (S3-SC). This T-cell subset interferes with the activity of S3-specific TS so that the latter cells can only be detected in situations where Tcs activity is deleted, e.g., by treatment of mice with cyclophosphamide (Cy). The mechanism by which Tcs regulate TS activity and requirements for induction of these cells are currently being investigated. In the PVP system, two subsets of TS have also been defined, and these appear to have several different characteristics from the TS induced by S3. We have also shown that very low (subimmunogenic) doses of PVP can activate specific helper T cells (TH), while doses of PVP that induce optimal antibody responses activate both TH and TS, although the latter predominate so that TH can be detected only when TS are eliminated. This suggests that, if TS activation can be reduced (or eliminated), some of the so-called TI antigens may behave similarly to T-dependent antigens. Since many of the bacterial pathogens, such as pneumococci and miningococci, elicit primarily TI-type antibody responses, it may therefore be possible to improve the efficacy of bacterial vaccines by immunizing under conditions that would favor THrather than TS activation. Our basic studies may ultimately prove to be applicable towards achieving such a goal. (LB)